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Northeast India with its rich and diverse avifauna acts as a hotbed for emerging virulent Newcastle disease virus (NDV) strains. The present work describes the molecular and pathogenic characterization of NDV strain isolated from Pandu, Assam, India. Clinicopathological and genetic analysis showed the virulent nature of NDV strain Pandu. On molecular phylogenetic and evolutionary distance analysis, the NDV strain Pandu formed a distinct clade within the genotype XIII of class II NDV, suggesting a new sub-genotype XIIIc. The accumulation of mutations in the NDV strain Pandu makes it divergent enough to be considered as a new sub-genotype. The proposed NDV sub-genotype XIIIc consists of strains recently reported from eastern and northeastern India. [ABSTRACT FROM AUTHOR]

Newcastle disease virus (NDV) is the causative agent of a highly contagious disease in avian species. All strains of NDV belong to avian paramyxovirus serotype-1. The disease is endemic in different parts of the world and vaccination is the only way to protect birds from NDV infection. The virus non-structural phosphoprotein (P) is the second most abundant protein and a major modulator of viral replication. Although P protein shows lesser evolutionary divergence among NDV isolates, it is known to be highly divergent among different avian paramyxovirus serotypes. In the present study, a recombinant P protein based single serum dilution ELISA was developed which showed better sensitivity, specificity and accuracy as compared to conventional methods for NDV detection. The recombinant P protein based ELISA could be an alternative to existing diagnostics against NDV infection in chickens. [ABSTRACT FROM AUTHOR]

Highlights: [•] Protective efficacy of gB, gC, and gD of ILTV was studied using NDV vector. [•] Three rNDVs expressing gB, gC, and gD of ILTV were constructed. [•] gD was most efficiently expressed and incorporated into envelope of rNDV. [•] ILTV gD is a major protective immunogen capable of inducing Nabs. [•] rNDV expressing ILTV gD offered complete protection against ILTV and NDV challenge. [ABSTRACT FROM AUTHOR]

Highlights • Imidazole was found to be the potential inhibitor of Newcastle disease virus (NDV) infection. • The imidazole derivative was found equally effective to reduce NDV infection in chicken. • The imidazole and its derivative specific activities could be due to modulation of type I interferon. Abstract Despite recent progress in vaccination options, Newcastle disease virus (NDV) stands a severe global epidemic and economic burden. It is difficult to control NDV with vaccination alone due to its evolving genetic variability; therefore, an effective therapeutic must target to resist its replication and further evolution. Drug repurposing is a practical and economical method to develop therapeutics against pathogenic organisms. Applying the knowledge of the broadly used antimicrobial activity of imidazole and its derivatives, we performed repurposing-based design of therapeutics to induce protection against NDV. We checked the ability of the compound at sub-lethal doses to reduce NDV replication in vitro , in ovo and in vivo. Chickens treated with the repurposed drug produced antiviral type I interferon and showed no shedding of the virus. Successful designing of novel NDV drug, in this study empirically demonstrates the principle that repurposing can be used for developing antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Classical swine fever virus (CSFV) is an etiological agent of classical swine fever. The structure protein E rns of CSFV assists in the initial attachment of the virus to the host cell and its subsequent entry. Newcastle disease virus (NDV) has been used as a virus vector to express different proteins successfully. The unique characters of NDV lying in its broad host spectrum and ease in production using embryonated chicken egg make it a choice of vector for expressing foreign gene. In the present work, we are reporting the characterization of the ribonuclease (RNase) activity of recombinant NDV expressing E rns of CSFV. The RNase activity of viral expressed recombinant E rns was found to be stable at a optimum temperature of 50 °C. The study will be useful to express and characterize an enzymatic protein in its native form using the NDV as a vector. [ABSTRACT FROM AUTHOR]

Abstract: The avian paramyxoviruses (APMVs) belong to the genus Avulavirus of family Paramyxoviridae. The APMVs are classified into nine serotypes on the basis of hemagglutination inhibition (HI) and neuraminidase inhibition (NI) assays, although some serologic cross-reaction exists. Newcastle disease virus (NDV), which constitutes serotype 1 (APMV-1), is an important pathogen of poultry, but the pathogenic potential of the other APMV serotypes is poorly understood. Although antibodies to APMV -2 to -9 are prevalent in chickens, the effect of prior exposure to these serotypes on susceptibility to NDV infection and disease was not known. In the present study, chickens were immunized with APMV-2 to -9 by the oculo-nasal route and later were challenged by the same route with a highly virulent strain of NDV. Among APMV-2 to -9, only APMV-3 induced serum antibodies that cross-reacted significantly with NDV and had significant NDV-neutralizing activity in vitro. In mock-immunized chickens, challenge NDV replicated throughout the respiratory tract as well as in the brain, spleen, and enteric tract. In contrast, in APMV-3-immunized chickens, challenge NDV replication was restricted to the upper respiratory tract and trachea. Some of the other APMVs also induced partial restriction of challenge NDV replication: for example, challenge NDV was not detected in the brains of APMV-9-immunized chickens, and shedding from the respiratory tract was reduced in chickens immunized with APMV-8 and -9. All of the chickens immunized with APMV-3 survived the NDV challenge; with APMV-2, -7, -8, and -9 the percentage survival was 30%, 20%, 20%, and 52.5%, respectively; whereas none of the chickens immunized with APMV-4, -5, or -6 survived. These results show that prior infection of chickens with APMV-3 induced substantial protection against NDV challenge, whereas prior infection with APMV-2, -7, -8, and -9 can alter subsequent NDV infection. The induction of NDV-neutralizing antibodies was a marker for efficient protection, but partial protection also was observed in their absence. [Copyright &y& Elsevier]

• Effect of Lithium chloride (LiCl) on Newcastle disease virus (NDV) replication in vitro , in ovo and in vivo. • Modulation of endoplasmic reticulum (ER) stress and stress inducive protein upon NDV infection. • Protective effect of LiCl against NDV-induced ER stress. Newcastle disease is a severe clinical manifestation of avian species caused by Newcastle disease virus (NDV). Although several vaccination strategies are available to protect poultry against NDV infection, even then, outbreaks have been reported in the vaccinated birds. The lack of therapeutics against NDV makes the need for effective anti-viral drugs is of utmost importance. Lithium Chloride (LiCl) is a widely prescribed drug for the treatment of bipolar disorder, acute brain injuries, and chronic neurodegenerative diseases. Also, LiCl has been repurposed as an effective anti-viral drug for some viral infections. In the present work, we have investigated the efficacy of LiCl to inhibit NDV replication using in vitro , in ovo, and in vivo models. Our results collectively showed the modulation of NDV replication after the LiCl treatment. We also demonstrated that NDV induces endoplasmic reticulum stress (ER-stress), and a stress-inducible ER chaperone, glucose-regulating protein 78 (GRP78), was found to be over-expressed after NDV infection. Subsequently, the treatment of NDV infected cells with LiCl significantly reduced the transcript and protein levels of GRP78. Finally, we concluded that LiCl treatment protects the cells from ER-stress induced by the NDV infection. [ABSTRACT FROM AUTHOR]

Newcastle disease virus (NDV) has been explored to a great extent to understand the biology of negative-sense RNA viruses. Nucleoprotein (N) is the most abundant protein in the virus particles, and its primary function is to encapsidate the virus genome for its transcription, replication, and packaging. Here, we report the structural investigations of the N protein of NDV (NDV-N) in solution. The N gene of NDV was cloned and expressed in E. coli as a soluble protein of ~53 kDa in size. The FE-TEM imaging of the purified NDV-N displayed a nearly spherical shape with a diameter of 28 nm and the DLS analysis of the purified NDV-N displayed a monodispersed nature, with averaged hydrodynamic radius, 26.5 nm. The conformational behavior of the NDV-N in solution was studied by SAXS analysis, which suggested two ring structures of NDV-N formed by thirteen monomeric units each. Each ring interacts with RNA molecules and forms a large molecule with a size of ~1450 kDa and are stacked on each other in a spiral arrangement. More profound knowledge of the N protein structure will help us in deciphering the control of viral RNA synthesis at the early stage of NDV life-cycle. [ABSTRACT FROM AUTHOR]

Japanese encephalitis (JE) is the most important cause of acute encephalitis syndrome (AES). Japanese encephalitis virus (JEV), the prototype member of the JE serocomplex, belongs to the genus Flavivirus. The immunogenic proteins envelope (E) and non-structural protein 1 (NS1) of JEV are widely explored for the development of vaccines and diagnostics against JEV. However, there are underlying concerns such as the risk of reversion of live-attenuated vaccines to high virulence, the incomplete inactivation of pathogens in inactivated vaccines and partial vaccine coverage. Newcastle disease virus (NDV) is an efficient viral vaccine vector to express several human and animal immunogenic proteins. In the present study, we have developed a recombinant NDV (rNDV), individually expressing the E and NS1 proteins of JEV (rNDV-Ejev and rNDV-NS1jev). The recovered rNDV-Ejev and rNDV-NS1jev were characterized in 9-day-old SPF embryonated chicken eggs and in cell culture. The vaccination of rNDV-Ejev and rNDV-NS1jev showed effective immunity against JEV upon intranasal immunization in BALB/c mice. The rNDVs vaccination produced effective neutralization antibody titers against both NDV and JEV. The cytokine profiling of the vaccinated mice showed an effective Th1 and Th2 mediated immune response. The study also provided an insight that E, when used in combination with NS1 could reduce the efficacy of only E based immunization in mice. Our results suggested rNDV-Ejev to be a promising live viral vectored vaccine against JEV. This study implies an alternative and economical strategy for the development of a recombinant vaccine against JEV. [ABSTRACT FROM AUTHOR]

Highlights: [•] Historical perspective and global scenario about Newcastle disease. [•] Characteristics about Newcastle disease virus genome. [•] Replication and pathogenicity of Newcastle disease virus. [•] Use of Newcastle disease virus as a vaccine vector. [•] Newcastle disease virus as an oncolytic agent. [Copyright &y& Elsevier]

Abstract: Avian paramyxoviruses (APMVs) belong to the genus Avulavirus in the family Paramyxoviridae and include at least nine serotypes, APMV-1 to -9, as well as two additional provisional serotypes. Newcastle disease virus (NDV), which comprises APMV-1, is the most extensively studied APMV because it is an important poultry pathogen. A moderate level of antigenic and genetic diversity is recognized for APMV-1 isolates, but our knowledge of the antigenic and genetic diversity of the other APMV serotypes is limited. APMV-4 is frequently isolated from waterfowl around the world. To date complete genome sequences of APMV-4 are available for only strains, which were isolated from ducks in Hong Kong, Korea and Belgium over a period of 37 years. We have carried out genome sequencing from the nucleocapsid (N) gene-end signal to the polymerase (L) gene-start signal of five APMV-4 strains recently isolated from Italy. Each of the eight APMV-4 strains has the same F protein cleavage site, DIQPR↓F. They also share a high level of nucleotide and amino acid sequence identity: for example, the F and HN glycoproteins have greater than 97% sequence identity between the various strains. Thus, comparison of these eight strains of APMV-4 did not provide evidence of substantial diversity, in contrast to similar studies with APMV-2, -3, and -6, in which the F and HN glycoproteins exhibited up to 20–30% amino acid sequence variation within a subgroup. Reciprocal cross-HI assay using post infection chicken sera also failed to detect significant antigenic variation among the available APMV-4 strains. [Copyright &y& Elsevier]